What does it sound like when a young researcher meets one of his science heroes for the first time? Listen to this episode of The AJP-Heart and Circ Podcast to find out. Associate Editor Dr. Keith Brunt (Dalhousie University) interviews author Dr. Holger Burchert (University of Basel) and leading expert Dr. William Stringer (Lundquist Institute at Harbor-UCLA Medical Center) about a new Methods and Resources article published by Burchert and Klimpel as part of the recent Call for Papers on Exercise, Physical Activity, and Cardiovascular Health. The article by Burchert et al. is an important contribution of methodological advancement built upon a foundation of established literature, dating back to Fick’s Principle, which first appeared as a two-paragraph conference abstract published in German in 1870 and later translated by The New England Journal of Medicine in 1948. Fick was the first to realize that cardiac output is equal to oxygen consumption divided by the arterial mixed venous oxygen content difference, allowing the first accurate determination of cardiac output. While non-invasive measurements of oxygen consumption and heart rate are now routine, sampling arterial and mixed venous blood is inherently challenging. This makes finding non-invasive techniques for these measurements incredibly important. Enter the OG of the linear method for determining the arterial mixed venous oxygen content difference, Dr. William Stringer. In his seminal 1997 article published in the Journal of Applied Physiology, “Cardiac output estimated noninvasively from oxygen uptake during exercise”, Dr. Stringer found that the arterial mixed venous oxygen content difference during incremental exercise can be estimated because it behaves in a predictable, linear fashion, thus avoiding the difficult blood sampling. Reading the article by Stringer et al., which was referenced in the CPET (cardiopulmonary exercise testing) machine manual Burchert used during his PhD work, sparked Burchert’s interest to investigate the literature and ultimately build on Stringer’s methodological approach by collaborating with this former school friend Dr. Fabian Klimpel. Burchert et al. found that a 3rd order polynomial S-curve described the arterial mixed venous oxygen content difference slightly better. More importantly, the authors also determined that the inflection point of this function could be related to the first ventilatory threshold and the inflection point of the oxygen dissociation curve. Why is this important? A deeper understanding of the mechanisms behind the s-shaped response has potential clinical translation, as the method could be further developed by tailoring it to individual patients. Listen as we discuss why it is important for early career researchers “to look back in order to look forward,” to use collaborators from other disciplines to support thinking creatively about cardiovascular physiology, and to align with mentors who facilitate young careers through constructive peer review and publication.

Holger Burchert and Fabian Klimpel Revisiting cardiac output estimated noninvasively from oxygen uptake during exercise: an exploratory hypothesis-generating replication study Am J Physiol Heart Circ Physiol, published August 25, 2023. DOI: 10.1152/ajpheart.00330.2023

William W. Stringer, James E. Hansen, and K. Wasserman Cardiac output estimated noninvasively from oxygen uptake during exercise J Appl Physiol, published March 1, 1997. DOI: 10.1152/jappl.1997.82.3.908

Fick, A On the Measurement of the Blood Quantum in the Ventricles of the Heart. Bauhaus-Universität Weimar, 1870, p. 16.